Over the past few years, a number of laboratories have become involved in determining the feasibility of utilizing the molecular techniques of gene therapy as part of the strategy for the treatment of human immunodeficiency virus (HIV) infection. One approach has been to transduce into peripheral blood CD4+ T cells selected genes of HIV which have been mutated and which can serve as trans-dominant mutants to block the expression of HIV if that cell ultimately became infected. Ideally, stem cells might be transduced and reinfused into the host thus providing a progeny of cells which are resistent to HIV infection or expression. Another approach to gene therapy has been to transduce into peripheral blood cells antisense HIV genes that when transcribed would bind to HIV mRNA and inhibit the production of HIV. In this regard, we have successfully transduced, using retroviral vectors, cell lines and peripheral blood lymphocytes with genes that express trans-dominant Rev mutants or antisense TAR RNA and have partially protected these cells against spreading HIV-1 infection.